Zoonotic and emerging infectious diseases represent an increasing and very real threat to global health, and it is essential that we expand our understanding of the pathogenesis and prevention of these diseases because of the increasing density of human populations, the increased exposure to domestic animal populations, and the crowding of wildlife into limited areas with frequent human contact. To address the need for infectious disease research capabilities, a COBRE Center of Excellence was established at Montana State University (MSU), with the goal of positioning Montana as a national leader in research on the pathogenesis of zoonotic infectious diseases. Over the past four years, the Center has been extremely successful, resulting in development of infrastructure, recruitment and support of junior investigators, and formation of a cohesive Center of investigators. The synergism of these components has resulted in the establishment of a solid foundation for expansion of infectious disease research in the region. With this infrastructure in place, we are now ideally poised to expand and strengthen the Center as a scalable and sustainable research enterprise. Our long term goal is to establish a sustainable Center of Excellence that is focused on understanding pathogenesis, host immune responses, and therapeutic development for zoonotic and emerging infectious diseases of regional and worldwide importance. While the foundation for this goal has been established through accomplishments realized during COBRE I, there is still a critical need for further faculty development, infrastructure enhancement, and recruitment of additional researchers in the area of zoonotic and emerging infectious diseases, and three specific aims are proposed to address these needs. First, we propose a pipeline to foster the development of current junior investigators so that funding and infrastructure resources are available at critical junctures in their careers. Secondly, we propose to increase the size, scope, and competitiveness of the Center through four new faculty hires. Together, accomplishment of these two aims will lead to establishment of the critical mass of investigators needed to sustain the Center and support future infectious disease research initiatives. Finally, we propose to strengthen the infectious disease research infrastructure in Montana through support and enhancement of established COBRE core facilities. Because of the success of COBRE I, the proven scientific abilities of the Center investigators, the outstanding institutional support, and the emphasis on a timely and increasingly important area of research, we believe that COBRE II support will lead to completion of a scalable and sustainable Center of Excellence in zoonotic and emerging infectious disease research.